| 10938438 |
Narita M, Ohsawa M, Mizoguchi H, Aoki T, Suzuki T, Tseng LF: Role of the phosphatidylinositol-specific phospholipase C pathway in delta-opioid receptor-mediated antinociception in the mouse spinal cord. Neuroscience. 2000;99(2):327-31.
Stimulation of delta-opioid receptors has been shown to activate phospholipase C via the activation of G-proteins in vitro. The present study was designed to determine, with the tail-flick method, whether the stimulatory effect of delta-opioid receptor agonists on phospholipase C and inositol lipid turnover participates in the mechanisms of the delta-opioid receptor-mediated antinociception in the mouse spinal cord. Intrathecal pretreatment with the phospholipase C inhibitors neomycin and U73122, which produced no changes in the basal tail-flick latencies when they were injected alone, significantly attenuated the antinociception induced by intrathecal administration of the selective delta-opioid receptor agonist [D-Ala (2)] deltorphin II in mice. The selective phosphatidylinositol-specific phospholipase C inhibitor ET-18-OCH (3) inhibited the antinociception induced by intrathecal administration of [D-Ala (2)] deltorphin II in a dose-dependent manner. In mice undergoing treatment with LiCl, which impairs phosphatidylinositol synthesis, the antinociception induced by intrathecal administration of [D-Ala (2)] deltorphin II was significantly reduced. Co-administration of D-myo-inositol-1,4,5-trisphosphate restored the [D-Ala (2)] deltorphin II-induced antinociception in LiCl-pretreated mice. On the other hand, intrathecal pretreatment with the selective protein kinase C inhibitor calphostin C, but not the protein kinase A inhibitor KT5720, resulted in a dose-dependent enhancement of the [D-Ala (2)] deltorphin II-induced antinociception. These results indicate a potential role for the phospholipase C-inositol-1,4, 5-trisphosphate pathway in the expression of delta-opioid receptor-mediated antinociception in the mouse spinal cord. Furthermore, activation of protein kinase C by the stimulation of delta-opioid receptors may constitute a significant pathway involved in negative modulation of spinal delta-opioid receptor-mediated antinociception. |
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